1.D.159.  The Fluorescent Barrel-Rosette M+/Cl- Channel (FBR-Ch) Family 

A series of 2-hydroxy-N (1),N (3)-diarylisophthalamide-based fluorescent ion channel-forming compounds have been synthesized and studied (Malla et al. 2020). Ion transport studies into large unilamellar vesicles confirmed that the compound with two 3,5-bis(trifluoromethyl)phenyl arms is the most efficient transporter among the series, and it facilitated both M+ and Cl- transport. The compound formed supramolecular ion channels with a single-channel conductance of 100 +/- 2 pS, a diameter of 5.06 +/- 0.16 Å and a permeability ratio, P Cl-/P K+ of 8.29 +/- 1. Molecular dynamics simulations of the proposed M2.11 channel (i.e. 11 coaxial layers of a dimeric rosette) with K+ and Cl- in the preequilibrated POPC lipid bilayer with water molecules illustrated various aspects of channel formation and ion permeation. Cell viability assays with the designed compounds indicated that cell death is induced by them, following the order of their ion transport activity with both chloride and cations playing roles in cell death. The inherent fluorescence of the most active transporter was helpful for monitoring its permeation in cells by confocal microscopy. The apoptosis-inducing activity upon perturbation of intracellular ionic homeostasis was established by monitoring mitochondrial membrane depolarization, the generation of reactive oxygen species, cytochrome c release, activation of the caspase 9 pathway, and finally the uptake of the propidium iodide dye in the treated cells (Malla et al. 2020).


 

References:

Malla, J.A., R.M. Umesh, A. Vijay, A. Mukherjee, M. Lahiri, and P. Talukdar. (2020). Apoptosis-inducing activity of a fluorescent barrel-rosette M/Cl channel. Chem Sci 11: 2420-2428.